tbuckley/cabot-search huggingface dataset:
Risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the SARS-CoV-2 variant Omicron BA.1-predominant period, Navarre, Spain, January to March 2022
Authors: Iván Martínez-Baz, Camino Trobajo-Sanmartín, Ana Miqueleiz, Itziar Casado, Ana Navascués, Cristina Burgui, Carmen Ezpeleta, Jesús Castilla, Marcela Guevara
Journal: Eurosurveillance (2023)

BackgroundAs COVID-19 vaccine effectiveness against SARS-CoV-2 infection was lower for cases of the Omicron vs the Delta variant, understanding the effect of vaccination in reducing risk of hospitalisation and severe disease among COVID-19 cases is crucial.AimTo evaluate risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the Omicron BA.1-predominant period in Navarre, Spain.MethodsA case-to-case comparison included COVID-19 epidemiological surveillance data in adults ≥ 18 years from 3 January-20 March 2022. COVID-19 vaccination status was compared between hospitalised and non-hospitalised cases, and between severe (intensive care unit admission or death) and non-severe cases using logistic regression models.ResultsAmong 58,952 COVID-19 cases, 565 (1.0%) were hospitalised and 156 (0.3%) were severe. The risk of hospitalisation was reduced within the first 6 months after full COVID-19 vaccination (complete primary series) (adjusted odds ratio (aOR): 0.06; 95% CI: 0.04-0.09) and after 6 months (aOR: 0.16; 95% CI: 0.12-0.21; pcomparison < 0.001), as well as after a booster dose (aOR: 0.06: 95% CI: 0.04-0.07). Similarly, the risk of severe disease was reduced (aOR: 0.13, 0.18, and 0.06, respectively). Compared with cases fully vaccinated 6 months or more before a positive test, those who had received a booster dose had lower risk of hospitalisation (aOR: 0.38; 95% CI: 0.28-0.52) and severe disease (aOR: 0.38; 95% CI: 0.21-0.68).ConclusionsFull COVID-19 vaccination greatly reduced the risk of hospitalisation and severe outcomes in COVID-19 cases with the Omicron variant, and a booster dose improved this effect in people aged over 65 years.
Decoding the genetic and epigenetic basis of asthma
Authors: Bernard S. Stikker, Rudi W. Hendriks, Ralph Stadhouders
Journal: Allergy (2023)

Abstract Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility is strongly influenced by genetics. Given its high prevalence and our incomplete understanding of the mechanisms underlying disease susceptibility, asthma is frequently studied in genome‐wide association studies (GWAS), which have identified thousands of genetic variants associated with asthma development. Virtually all these genetic variants reside in non‐coding genomic regions, which has obscured the functional impact of asthma‐associated variants and their translation into disease‐relevant mechanisms. Recent advances in genomics technology and epigenetics now offer methods to link genetic variants to gene regulatory elements embedded within non‐coding regions, which have started to unravel the molecular mechanisms underlying the complex (epi)genetics of asthma. Here, we provide an integrated overview of (epi)genetic variants associated with asthma, focusing on efforts to link these disease associations to biological insight into asthma pathophysiology using state‐of‐the‐art genomics methodology. Finally, we provide a perspective as to how decoding the genetic and epigenetic basis of asthma has the potential to transform clinical management of asthma and to predict the risk of asthma development.
Stopping the fat: Repurposing an antidepressant for cancer treatment
Authors: Deepika Bhullar, Cosimo Commisso
Journal: The Journal of Experimental Medicine (2023)

In this issue of JEM, Chu and An et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20221316) describe the role of the tricyclic antidepressant nortriptyline in inhibition of fatty acid uptake. Nortriptyline promotes cell acidification and suppresses macropinocytosis, providing a link between fatty acid uptake and tumor progression.
Association of Radiation and Procarbazine Dose With Risk of Colorectal Cancer Among Survivors of Hodgkin Lymphoma
Authors: Yvonne M. Geurts, Rebecca Shakir, Georgios Ntentas, Sander Roberti, Marianne C. Aznar, Katinka M. John, Johanna Ramroth, Cécile P. M. Janus, Augustinus D. G. Krol, Judith M. Roesink, Richard W. M. van der Maazen, Josée M. Zijlstra, Sarah C. Darby, Berthe M. P. Aleman, Flora E. van Leeuwen, David J. Cutter, Michael Schaapveld
Journal: JAMA Oncology (2023)

Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear.To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022.Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored.The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose.This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.
Comparing the Hospital Frailty Risk Score and the Clinical Frailty Scale Among Older Adults With Chronic Obstructive Pulmonary Disease Exacerbation
Authors: Melanie Chin, Tetyana Kendzerska, Jiro Inoue, Michael Aw, Linda Mardiros, Christopher Pease, Melissa K. Andrew, Smita Pakhale, Alan J. Forster, Sunita Mulpuru
Journal: JAMA Network Open (2023)

Frailty is associated with severe morbidity and mortality among people with chronic obstructive pulmonary disease (COPD). Interventions such as pulmonary rehabilitation can treat and reverse frailty, yet frailty is not routinely measured in pulmonary clinical practice. It is unclear how population-based administrative data tools to screen for frailty compare with standard bedside assessments in this population.To determine the agreement between the Hospital Frailty Risk Score (HFRS) and the Clinical Frailty Scale (CFS) among hospitalized individuals with COPD and to determine the sensitivity and specificity of the HFRS (vs CFS) to detect frailty.A cross-sectional study was conducted among hospitalized patients with COPD exacerbation. The study was conducted in the respiratory ward of a single tertiary care academic hospital (The Ottawa Hospital, Ottawa, Ontario, Canada). Participants included consenting adult inpatients who were admitted with a diagnosis of acute COPD exacerbation from December 2016 to June 2019 and who used a clinical care pathway for COPD. There were no specific exclusion criteria. Data analysis was performed in March 2022.Degree of frailty measured by the CFS.The HFRS was calculated using hospital administrative data. Primary outcomes were the sensitivity and specificity of the HFRS to detect frail and nonfrail individuals according to CFS assessments of frailty, and the secondary outcome was the optimal probability threshold of the HFRS to discriminate frail and nonfrail individuals.Among 99 patients with COPD exacerbation (mean [SD] age, 70.6 [9.5] years; 56 women [57%]), 14 (14%) were not frail, 33 (33%) were vulnerable, 18 (18%) were mildly frail, and 34 (34%) were moderately to severely frail by the CFS. The HFRS (vs CFS) had a sensitivity of 27% and specificity of 93% to detect frail vs nonfrail individuals. The optimal probability threshold for the HFRS was 1.4 points or higher. The corresponding sensitivity to detect frailty was 69%, and the specificity was 57%.In this cross-sectional study, using the population-based HFRS to screen for frailty yielded poor detection of frailty among hospitalized patients with COPD compared with the bedside CFS. These findings suggest that use of the HFRS in this population may result in important missed opportunities to identify and provide early intervention for frailty, such as pulmonary rehabilitation.
10-Year Outcomes of Catheter-Based Renal Denervation in Patients With Resistant Hypertension
Authors: Hussam Al Ghorani, Saarraaken Kulenthiran, Michael Johannes Maria Recktenwald, Lucas Lauder, Michael Kunz, Felix Götzinger, Sebastian Ewen, Christian Ukena, Michael Böhm, Felix Mahfoud
Journal: Journal of the American College of Cardiology (2023)
Dysregulation of CD177 <sup>+</sup> neutrophils on intraepithelial lymphocytes exacerbates gut inflammation via decreasing microbiota-derived DMF
Authors: Huimin Chen, Xiaohan Wu, Ruicong Sun, Huiying Lu, Ritian Lin, Xiang Gao, Gengfeng Li, Zhongsheng Feng, Ruixin Zhu, Yao Yao, Baisui Feng, Zhanju Liu
Journal: Gut Microbes (2023)

Neutrophils synergize with intestinal resident intraepithelial lymphocytes (IELs) to serve as the first-line defense and maintain intestinal homeostasis. However, the underlying mechanisms whereby neutrophils regulate IELs to inhibit intestinal inflammation are still not completely understood. Here, we found that depletion of neutrophils (especially CD177
PET/CT Manifestations of a Case of Penicilliosis Marneffei Misdiagnosed as Lung Cancer
Authors: You Cheng, Wen-min Li, Shu-xia Wang, Dan Shao
Journal: Clinical Nuclear Medicine (2023)

Penicilliosis marneffei is an extremely rare fungal infectious disease and is especially rare in people with normal immunity. Penicilliosis marneffei restricted to the lung and involving the formation of a pulmonary tumor is difficult to distinguish from peripheral lung cancer. This kind of case has rarely been reported. We report the case of a 53-year-old man with penicilliosis marneffei misdiagnosed as lung cancer by 18 F-FDG PET/CT.
Letter to the Editor: Novel antidiabetic drugs and the risk for HCC. What else to expect from these “wonderful” drug classes?
Authors: Dimitrios Patoulias
Journal: Hepatology (2023)

To the editor, In the latest issue of Hepatology, Plaz Torres et al.1 describe in detail the effect of all currently available antidiabetic drug classes on HCC. Recent epidemiologic data are highly supportive of the beneficial effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on mortality among subjects with an established diagnosis of HCC and type 2 diabetes mellitus2; SGLT-2 inhibitors provided a significant decrease in the risk for HCC-related death by 32%, with duration of use more than a year resulting in a significant reduction in the corresponding risk by 40%. Of note, concurrent use of metformin provided an additional mortality benefit versus SGLT-2 inhibitor use alone.2 This study suggested that even among patients with a definite diagnosis of HCC, initiation of SGLT-2 inhibitor might improve overall mortality, if the patient is eligible for this drug class.2 It is also known that patients with NAFLD and type 2 diabetes mellitus may progress to advanced liver fibrosis and finally cirrhosis, while for those with established cirrhosis there is an increased risk for HCC.3 It has been formerly shown in another epidemiologic study that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in subjects with cirrhosis and type 2 diabetes mellitus resulted in a significant decrease in the risk for cirrhosis decompensation.4 Of note, decompensation rates were similar between users of SGLT-2 inhibitors and GLP-1RAs, confirming the beneficial effects of both drug classes in patients with established, compensated cirrhosis.4 Therefore, it seems that besides their cardioprotective and renoprotective effects, both SGLT-2 inhibitors and GLP-1RAs are beneficial for patients with cirrhosis, an independent risk factor for HCC development, and for patients with confirmed HCC. It appears that the characterization of SGLT-2 inhibitors as "the statins of the 21st century" by Braunwald5 is rather realistic, than provocative, while this characterization could be extended to GLP-1RAs, which have provided impressive results in different clinical settings. Of course, underlying mechanisms for those beneficial effects in cirrhosis and HCC have to be thoroughly investigated, and confirmed in future, dedicated studies.
Transcatheter Edge-to-Edge Repair in Patients With Anatomically Complex Degenerative Mitral Regurgitation
Authors: Jörg Hausleiter, D. Scott Lim, Linda D. Gillam, Firas Zahr, Scott Chadderdon, Andrew N. Rassi, Raj Makkar, Scott Goldman, Volker Rudolph, James Hermiller, Robert M. Kipperman, Abhijeet Dhoble, Richard Smalling, Azeem Latib, Susheel K. Kodali, Mohamad Lazkani, Joseph Choo, Philipp Lurz, William W. O’Neill, Roger Laham, Josep Rodés-Cabau, Saibal Kar, Niklas Schofer, Brian Whisenant, Ignacio Inglessis-Azuaje, Stephan Baldus, Samir Kapadia, Konstantinos Koulogiannis, Leo Marcoff, Robert L. Smith
Journal: Journal of the American College of Cardiology (2023)
Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews
Authors: Giovanni E Ferreira, Christina Abdel-Shaheed, Martin Underwood, Nanna B Finnerup, Richard O Day, Andrew McLachlan, Sam Eldabe, Joshua R Zadro, Christopher G Maher
Journal: BMJ (2023)

Abstract Objective To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition. Design Overview of systematic reviews. Data sources PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022. Eligibility criteria for selecting studies Systematic reviews comparing any antidepressant with placebo for any pain condition in adults. Data extraction and synthesis Two reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework. Results 26 reviews (156 unique trials and &gt;25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference −5.3, 95% confidence interval −7.3 to −3.3), postoperative pain (−7.3, −12.9 to −1.7), neuropathic pain (−6.8, −8.7 to −4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons). Conclusions Evidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews—seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions. Systematic review registration PROSPERO CRD42022311073.
Increased Tumor Mutation Burden Levels and Sensitivity of Non–Small Cell Lung Cancer to PD-L1 Blockade—Reply
Authors: Biagio Ricciuti, Xinan Wang, Mark M. Awad
Journal: JAMA Oncology (2023)

In Reply We thank Aslan et al and Zhang and Zhang for their interest in our cohort study on the association of tumor mutation burden (TMB) with clinical outcomes to programmed cell death–1 (PD-1) or PD-1 ligand (PD-L1) blockade across PD-L1 expression levels in non–small cell lung cancer (NSCLC).1
Condensate biology of synaptic vesicle clusters
Authors: Roberto Sansevrino, Christian Hoffmann, Dragomir Milovanovic
Journal: Trends in Neurosciences (2023)

Neuronal communication crucially relies on exocytosis of neurotransmitters from synaptic vesicles (SVs) which are clustered at synapses. To ensure reliable neurotransmitter release, synapses need to maintain an adequate pool of SVs at all times. Decades of research have established that SVs are clustered by synapsin 1, an abundant SV-associated phosphoprotein. The classical view postulates that SVs are crosslinked in a scaffold of protein-protein interactions between synapsins and their binding partners. Recent studies have shown that synapsins cluster SVs via liquid-liquid phase separation (LLPS), thus providing a new framework for the organization of the synapse. We discuss the evidence for phase separation of SVs, emphasizing emerging questions related to its regulation, specificity, and reversibility.
Bone Scan With Pulmonary Uptake in Scleroderma
Authors: Fatemeh Farahmandfar, Sadegh Moradian, Mehran Pournazari, Mehdi Salimi, Sara Shakeri
Journal: Clinical Nuclear Medicine (2023)

We present a 61-year-old woman with a history of scleroderma and suspicion of osteomyelitis in her left wrist. She underwent a 3-phase bone scan for evaluation of osteomyelitis. Incidentally, the scan showed bilateral pulmonary MDP uptake, especially in lower lobes, which was proven to be due to the nonfibrotic form of nonspecific interstitial pneumonia.
Nodular Fasciitis
Authors: Marika A. Pitot, Stephen M. Broski, Scott M. Thompson, David A. Woodrum, Garret M. Powell
Journal: Clinical Nuclear Medicine (2023)

PET/CT plays a crucial role in the management of prostate cancer with several emerging and established radiopharmaceuticals, including 18 F-piflufolastat and 11 C-choline. These radiotracers are thought to be relatively specific to prostate cancer; however, uptake has also been demonstrated in other benign and malignant lesions. Nodular fasciitis is a rapidly growing benign soft tissue neoplasm that is typically self-limiting. Although a few case reports describe 68 Ga-PSMA uptake in nodular fasciitis, uptake of 11 C-choline and other PSMA-targeted PET probes, including 18 F-piflufolastat, have not previously been reported. We present a novel case of nodular fasciitis demonstrating both 18 F-piflufolastat and 11 C-choline avidity.
Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications
Authors: Paula Fernández-Palanca, Tania Payo-Serafín, Carolina Méndez-Blanco, Beatriz San-Miguel, María J Tuñón, Javier González-Gallego, José L Mauriz
Journal: Clinical and Molecular Hepatology (2023)

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.
Inhibition of phosphoglycerate kinase 1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism
Authors: Yang Lu, Ning Zhao, Yuwei Wu, Shuaitao Yang, Qiongfeng Wu, Qian Dong, Yimei Du
Journal: Cardiovascular Research (2023)

Abstract Aims CD4+ T cells are the major drivers of cardiac-specific autoimmunity in myocarditis, specifically Th1, Treg, and most significant Th17 cells. But the molecular mechanisms of their activation remain unclear. We aimed to elucidate the regulatory role of phosphoglycerate kinase 1 (PGK1) in CD4+ T cells and experimental autoimmune myocarditis (EAM). Methods and results EAM was induced in BALB/c mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified in complete Freund’s adjuvant. Single-cell sequencing analysis found that glycolysis and PGK1 expression were elevated in cardiac CD4+ T and Th17 cells from myocarditis mice. Mice treated with PGK1 inhibitor NG52 showed less cardiac inflammation and fibrosis and better contractile function, as well as reduced cardiac infiltrating Th17 and Th1 cells and increased proportion of Treg. NG52 suppressed CD4+ T cell activation and differentiation of mice and myocarditis patients in vitro. Mechanistically, inhibition of PGK1 suppressed glycolytic activity and decreased pyruvate dehydrogenase kinase 1 (PDHK1) phosphorylation, thereby increasing reactive oxygen species (ROS) production in mitochondria and thus preventing Th17 cell differentiation. Conclusion PGK1 may act as a key metabolic regulator of CD4+ T cell differentiation and regulates Th17 cell differentiation by regulating glycolysis and the PDHK1-ROS axis. Targeting PGK1 might be a promising strategy for the treatment of myocarditis.